Valve block assembly

ABSTRACT

A device to enhance sealing is provided. The device includes a body and a pressure cup. The pressure cup includes a channel, a first pressure channel, and a second pressure channel. The channel is formed in a surface of the body to surround a first portion of the surface. The channel is configured to hold an o-ring. The first pressure channel extends through the body and opens into the first portion of the surface. The second pressure channel extends through the body and opens into the channel. Pneumatic pressure within the second pressure channel is controlled to hold the o-ring in the channel when a second pressure within the first pressure channel changes.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 12/194,927, filed Aug. 20, 2008, now allowed, issuing on Jun.12, 2012, as U.S. Pat. No. 8,196,603 and is hereby incorporated byreference in its entirety.

BACKGROUND

Simulated moving bed chromatography (SMB) utilizes a number ofinterconnecting separation beds containing solid phase chromatographysubstrates. Inlet ports for feedstock and desorbent and outlet ports forraffinate and extract are placed at specific points in the series ofseparation beds, and a series of valves and tubing and/or channelsconnects flow to provide a continuous loop. Liquid flow is controlled bytwo or more pumps connected to the inlet and/or outlet streams. Atdefined intervals, the positions of the inlet and outlet ports areswitched in the same direction as the flow, simulating a countercurrentmovement of the solid phase beds relative to the fluid streams.Feedstock introduced into the first bed begins to separate intocomponents contained therein as flow ensues, with less retained speciesmigrating in the direction of fluid flow and being collected at theraffinate port. The more retained species remain preferentiallyassociated with the solid phase and are collected at the extract port.By regulating the switch times and flow rates of feedstock, desorbent,raffinate, and extract, a standing wave pattern is established, allowingfor continuous flow of purified products from the system.

The principle of continuous countercurrent chromatography relies on thephenomenon of preferential retention on an immobilized sorbent substrateof one or more substances in a feedstock mixture, separation of lessretained substances, and subsequent recovery of the separatedsubstances. In standard SMB, this process is repeated in a succession ofcolumns by switching zones of separation, enrichment, and regenerationin stepwise sequence using a valve system.

For large scale industrial systems, the bed volume is so great comparedto void volumes of liquid between beds that even elaborate valve systemsinvolving extensive conduits do not interfere with the process. Therehas been a recent trend, however, in scaling SMB down to pilot andsub-pilot volumes, as the need for more sophisticated applications hasarisen in the fine chemicals and pharmaceutical fields requiringmilligram-to-gram level quantities of product. For example, the ProteinStructure Initiative is a national effort to determine thethree-dimensional structure of a wide variety of proteins. Thisinitiative will accelerate the discovery of protein function and enablefaster development of new therapies for treating genetic and infectiousdiseases. One of the significant challenges is to develop methods ofpurifying target proteins from complex cell extracts in small (10-100milligram) quantities, in high purity (greater than 90%). SMB scaleddown in size promises to provide a mechanism for overcoming thesechallenges.

SUMMARY

In an exemplary embodiment, a device to enhance sealing is provided. Thedevice includes, but is not limited to, a body and a pressure cup. Thepressure cup includes, but is not limited to, a channel, a firstpressure channel, and a second pressure channel. The channel is formedin a surface of the body to surround a first portion of the surface. Thechannel is configured to hold an o-ring. The first pressure channelextends through the body and opens into the first portion of thesurface. The second pressure channel extends through the body and opensinto the channel. Pneumatic pressure within the second pressure channelis controlled to hold the o-ring in the channel when a second pressurewithin the first pressure channel changes.

In another exemplary embodiment, a fluidics stack assembly is provided.The fluidics stack assembly includes, but is not limited to, aninput/output (I/O) plate, fluidics plate, and a seal plate. The I/Oplate includes, but is not limited to, an inlet port hole and an outletport hole extending through the I/O plate. The fluidics plate includes,but is not limited to, a first surface comprising an inlet channelformed in the first surface and an outlet hole extending through thefluidics plate and a second surface comprising an inlet hole, the outlethole, and a first channel formed in the second surface. The inletchannel includes the inlet hole which extends through the fluidicsplate. The seal plate includes, but is not limited to, a first hole anda second hole extending through the seal plate. The I/O plate, thefluidics plate, and the seal plate are aligned and mounted to form asealing surface between the I/O plate and the fluidics plate and betweenthe fluidics plate and the seal plate. When aligned, the inlet port holealigns with the inlet channel, the inlet hole aligns with the firsthole, the outlet port hole aligns with the outlet hole, and the secondhole aligns with the first channel to support fluid communicationbetween the inlet port hole and the outlet port hole.

In another exemplary embodiment, a valve block assembly is provided. Thevalve block assembly includes, but is not limited to, a fluidics stackassembly, a membrane, and a pressure cup plate. The fluidics stackassembly includes, but is not limited to, an input/output (I/O) plate,fluidics plate, and a seal plate. The I/O plate includes, but is notlimited to, an inlet port hole and an outlet port hole extending throughthe I/O plate. The fluidics plate includes, but is not limited to, afirst surface comprising an inlet channel formed in the first surfaceand an outlet hole extending through the fluidics plate and a secondsurface comprising an inlet hole, the outlet hole, and a first channelformed in the second surface. The inlet channel includes the inlet holewhich extends through the fluidics plate. The seal plate includes, butis not limited to, a first hole and a second hole extending through theseal plate. The I/O plate, the fluidics plate, and the seal plate arealigned and mounted to form a sealing surface between the I/O plate andthe fluidics plate and between the fluidics plate and the seal plate.When aligned, the inlet port hole aligns with the inlet channel, theinlet hole aligns with the first hole, the outlet port hole aligns withthe outlet hole, and the second hole aligns with the first channel tosupport fluid communication between the inlet port hole and the outletport hole. The pressure cup plate includes, but is not limited to, apressure cup. The pressure cup includes, but is not limited to, ano-ring, a channel formed in a surface of the pressure cup plate tosurround a first portion of the surface, and a first pressure channelextending through the body and opening into the first portion of thesurface. The channel is configured to hold the o-ring. The fluidicsstack assembly, the membrane, and the surface of the pressure cup plateare aligned and mounted to form a sealing surface between the I/O plateand the fluidics plate, between the fluidics plate and the seal plate,between the seal plate and the membrane, and between the membrane andthe surface of the pressure cup plate. When aligned, the inlet port holealigns with the inlet channel, the inlet hole aligns with the firsthole, the outlet port hole aligns with the outlet hole, and the secondhole aligns with the first channel, and the first portion of the surfaceof the pressure cup plate surrounds the first hole and the second holeto support fluid communication between the inlet port hole and theoutlet port hole under control of pressure changes within the firstpressure channel.

Other principal features and advantages of the invention will becomeapparent to those skilled in the art upon review of the followingdrawings, the detailed description, and the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments of the invention will hereafter be described withreference to the accompanying drawings, wherein like numerals denotelike elements.

FIG. 1 shows a perspective view of an SMB system in accordance with anexemplary embodiment.

FIG. 2 shows an assembled, perspective view of a right valve blockassembly of the SMB system of FIG. 1 in accordance with an exemplaryembodiment.

FIG. 3 shows a disassembled, exploded, perspective view of a right valveblock assembly of the SMB system of FIG. 1 in accordance with anexemplary embodiment.

FIG. 4 shows a block diagram of a control system of the SMB system ofFIG. 1 in accordance with an exemplary embodiment.

FIG. 5 shows a front view of a port plate of the right valve blockassembly of FIG. 3 in accordance with an exemplary embodiment.

FIG. 6 shows a front, perspective view of a fluidics stack assembly ofthe right valve block assembly of FIG. 3 in accordance with an exemplaryembodiment.

FIG. 7 shows a front face of a fluidics plate of the fluidics stackassembly of FIG. 6 in accordance with an exemplary embodiment.

FIG. 8 shows a back face of the fluidics plate of FIG. 7 in accordancewith an exemplary embodiment.

FIG. 9 shows a front, perspective view of a seal plate of the fluidicsstack assembly of FIG. 6 in accordance with an exemplary embodiment.

FIG. 10 shows a front view of a pressure cup plate of the right valveblock assembly of FIG. 3 in accordance with an exemplary embodiment.

FIG. 11 shows a back view of the pressure cup plate of FIG. 10 inaccordance with an exemplary embodiment.

FIG. 12 shows a cross sectional view of the pressure cup plate of FIG.10 in accordance with an exemplary embodiment.

FIG. 13 shows a blowup cross sectional view of a portion of the pressurecup plate of FIG. 12 in accordance with an exemplary embodiment.

FIG. 14 shows a blowup view of a portion of a front face of the pressurecup plate of FIG. 10 in accordance with an exemplary embodiment.

FIG. 15 shows a side, cutaway view of an o-ring used in the pressure cupplate of FIG. 10 in accordance with an exemplary embodiment.

FIG. 16 shows a blowup cross sectional view of the o-ring of FIG. 15 inaccordance with an exemplary embodiment.

FIG. 17 shows a front, perspective view of a thermal isolation plate ofthe right valve block assembly of FIG. 3 in accordance with an exemplaryembodiment.

FIG. 18 shows a front view of a valve manifold of the right valve blockassembly of FIG. 3 in accordance with an exemplary embodiment.

FIG. 19 shows a right side view of the valve manifold of FIG. 18 inaccordance with an exemplary embodiment.

FIG. 20 shows a left side view of the valve manifold of FIG. 18 inaccordance with an exemplary embodiment.

FIG. 21 shows a back side view of the valve manifold of FIG. 18 inaccordance with an exemplary embodiment.

FIG. 22 illustrates the fluidics flow between the left and the rightvalve block assemblies in accordance with an exemplary embodiment.

FIG. 23 shows a front side, perspective view of a column rack assemblyof the SMB system of FIG. 1 in accordance with an exemplary embodiment.

FIG. 24 shows a back side, perspective view of the column rack assemblyof FIG. 23 in accordance with an exemplary embodiment.

FIG. 25 shows a front side, perspective view of a mounting plate of thecolumn rack assembly of FIG. 23 in accordance with an exemplaryembodiment.

FIG. 26 shows a front side, perspective view of a clamping drawer of thecolumn rack assembly of FIG. 23 in accordance with an exemplaryembodiment.

FIG. 27 shows a cross-sectional view of a rack of the column rackassembly of FIG. 23 in accordance with an exemplary embodiment.

FIG. 28 shows a front, skeleton view of a spring block of the columnrack assembly of FIG. 23 in accordance with an exemplary embodiment.

FIG. 29 shows a bottom, skeleton view of the spring block of FIG. 27 inaccordance with an exemplary embodiment.

DETAILED DESCRIPTION

With reference to FIG. 1, a perspective view of an SMB system 100 isshown in accordance with an exemplary embodiment. SMB system 100 mayinclude a housing 102. Housing 102 may have a variety of shapes andsizes based on the components housed therein. In the exemplaryembodiment of FIG. 1, housing 102 has a generally cubic shape. Housing102 may include a front side panel 103 and a left side panel 110 inaddition to other panels not further discussed. Front side panel 103 mayinclude a number of panels organized to present information to the userand to provide access to various components of SMB system 100 to theuser. For example, front side panel 103 may include an electronics panel104, an inlet/outlet (I/O) port panel 105, a pump panel 106, and a valveblock panel 108.

Electronics panel 104 may include a column status indicator interface112 and an on/off switch 114. Column status indicator interface 112indicates a status of each chromatographic column of SMB system 100. Inthe exemplary embodiment of FIG. 1, column status indicator interface112 indicates a status for eight chromatographic columns shown inseparate columns though any number of chromatographic columns may beused depending on the application. Using on/off switch 114, the userturns on or off SMB system 100.

I/O port panel 105 may include a plurality of inlet port connectors 128for providing fluid to SMB system 100 and a plurality of outlet portconnectors 130 for collecting fluid from SMB system 100. In theexemplary embodiment of FIG. 1, I/O port panel 105 includes four inletport connectors 128 and four outlet port connectors 130 though anynumber of port connectors may be used depending on the application.

Pump panel 106 may include a plurality of pump heads 132 and a pluralityof pump control interfaces 133 with a pump control interface associatedwith each pump head. Fluid provided to SMB system 100 can be connectedto a pump head of the plurality of pump heads 132. The fluid may beprovided from the plurality of pump heads 132 to an inlet port connectorof the plurality of inlet port connectors 128 at an appropriate flowrate as selected by the user. The user can adjust various parametersassociated with a selected pump such as the flow rate using a respectivepump control interface of the plurality of pump control interfaces 133.In an exemplary embodiment, the pump head is associated with ahigh-pressure, piston pump. In the exemplary embodiment of FIG. 1, pumppanel 106 includes four pump heads 132 though any number of pump headsmay be used depending on the application. Pumps may also be controlledvia a separate computer using appropriate interface hardware andsoftware. Other types of pump, including, but not limited toperistaltic, syringe, or gear pumps can be used with the system.

Valve block panel 108 may include a left panel cover plate 116, a rightpanel cover plate 118, a column rack assembly 120, a first pressuregauge 122, a second pressure gauge 124, a first plurality of column portconnectors 126, and a second plurality of column port connectors 204(shown with reference to FIG. 2). Left panel cover plate 116 is a coverplate mounted in front of a left valve block assembly. As used herein,the term “mount” includes join, unite, connect, associate, insert, hang,hold, affix, attach, fasten, bind, paste, secure, bolt, screw, rivet,solder, weld, press against, and other like terms. Right panel coverplate 118 is a cover plate mounted in front of a right valve blockassembly 200 (shown with reference to FIG. 2). Column rack assembly 120is mounted between left side panel cover plate 116 and right panel coverplate 118. Chromatographic columns are mounted to column rack assembly120 and are connected to the left valve block assembly using the firstplurality of column port connectors 126 and to right valve blockassembly 200 using the second plurality of column port connectors 204.In the exemplary embodiment of FIG. 1, column rack assembly 120 providesmounting locations for eight chromatographic columns though any numberof chromatographic columns may be used depending on the application. Asan example, in a typical SMB application, at least three or fourchromatographic columns may be used.

First pressure gauge 122 may indicate a pressure associated with a firstpneumatic pressure system, and second pressure gauge 124 may indicate apressure associated with a second pneumatic pressure system. Forexample, first pressure gauge 122 may be associated with a gas pressuresystem for an o-ring system and second pressure gauge 124 may beassociated with a gas pressure system for a valve system. In theexemplary embodiment of FIG. 1, two separate pressure systems are used;however, this is not necessary as a smaller or a larger number ofpressure systems may be used.

Left side panel 110 may include a first pressure regulator 134 tocontrol a pneumatic pressure associated with the first pressure system,and a second pressure regulator 136 to control a pneumatic pressureassociated with the second pressure system. The pneumatic pressure maybe provided using an inert gas pressurized tank or tanks containingeither nitrogen, helium, or other suitable gas, or by a suitable aircompressor.

With reference to FIG. 2, an assembled, perspective view of right valveblock assembly 200 of SMB system 100 is shown in accordance with anexemplary embodiment. The left valve block assembly (not shown) behindleft side panel cover plate 116 is equivalent to right valve blockassembly 200, but is rotated 180 degrees relative to right valve blockassembly 200. The left valve block assembly may connect through thechromatographic columns mounted to column rack assembly 120 to rightvalve block assembly 200. The side by side mounting of left valve blockassembly and right valve block assembly 200 simplifies the connectionsbetween the valve blocks.

Right valve block assembly 200 may include a port plate 202, a pressurecup plate 210, a thermal isolation plate 212, a valve manifold 214, afirst plurality of valves 216, a second plurality of valves 217, and anelectronics board 218. Port plate 202 includes the second plurality ofcolumn port connectors 204, a plurality of inlet port connectors 206,and a plurality of outlet port connectors 208. The plurality of inletport connectors 206 can be connected to the plurality of inlet portconnectors 128 to provide a fluid path between the inlet portconnectors. The plurality of outlet port connectors 208 can be connectedto the plurality of outlet port connectors 130 to provide a fluid pathbetween the outlet port connectors. The first plurality of valves 216are positioned on a right side face 1900 (shown with reference to FIG.19) of valve manifold 214 and the second plurality of valves 217 arepositioned on a left side face 2000 (shown with reference to FIG. 20) ofvalve manifold 214 wherein the first side and the second side of valvemanifold 214 face in opposite directions.

Electronics board 218 mounts to a back face of valve manifold 214.Electronics board 218 includes a plurality of electrical connectors 220that, when connected at both ends, provide an electrical signal to thefirst plurality of valves 216 with each connector of the plurality ofelectrical connectors 220 connecting to a valve of the first pluralityof valves 216. Corresponding electrical connectors are mounted to theopposite side of electronics board 218 to connect to the secondplurality of valves 217. In an exemplary embodiment, the first pluralityof valves 216 and the second plurality of valves 217 are solenoid valvesconfigured to operate in a pressure range up to 300 pounds per squareinch (psi). Other pressure ranges, including but not limited to 0-100psi, 0-150 psi, 0-200 psi, 0-400 psi, and higher ranges may also beused.

With reference to FIG. 3, a disassembled, exploded, perspective view ofright valve block assembly 200 of SMB system 100 is shown in accordancewith an exemplary embodiment. Right valve block assembly 200 may includea valve block 300, the first plurality of valves 216, the secondplurality of valves 217, and electronics board 218. Valve block 300 mayinclude port plate 202, fluidics stack assembly 302, a membrane 304, aplurality of o-rings 306, pressure cup plate 210, a first gasket plate308, thermal isolation plate 212, a second gasket plate 310, and valvemanifold 214. A plurality of first connectors 312 and second connectors313 mount port plate 202 to pressure cup plate 210 and to valve manifold214 to provide a sealing surface between each of the components of valveblock 300. A plurality of third connectors 318 mount electronics board218 to the back face of valve manifold 214.

The plurality of o-rings 306 are positioned within corresponding o-ringchannels 1008 (shown with reference to FIG. 10) of pressure cup plate210 to facilitate sealing between membrane 304, pressure cup plate 210,and fluidics stack assembly 302. Fluid flow within SMB system 100 ismaintained between the second plurality of column port connectors 204,the plurality of inlet port connectors 206, and the plurality of outletport connectors 208 of port plate 202 and fluidics stack assembly 302 bymembrane 304. Pneumatic pressure provided to SMB system 100 ismaintained between the first pneumatic pressure system and the secondpneumatic pressure system and pressure cup plate 210, first gasket plate308, thermal isolation plate 212, second gasket plate 310, and valvemanifold 214 by membrane 304 which separates the fluidic and pneumaticsystems of SMB system 100.

Port plate 202, fluidics stack assembly 302, membrane 304, and pressurecup plate 210 are aligned using dowel pins 314. Dowel pins 314 extendinto a bore in a back face of port plate 202, through respective boresin fluidics stack assembly 302 and membrane 304, and into a bore 1012(shown with reference to FIG. 10) in a recessed face 1000 (shown withreference to FIG. 10) of pressure cup plate 210 when properly aligned.Port plate 202, fluidics stack assembly 302, membrane 304, and recessedface 1000 of pressure cup plate 210 are mounted adjacent to each otherin that order as shown with reference to FIG. 3. Fluidics stack assembly302, and membrane 304 are positioned within a cavity formed in frontface 1001 (shown with reference to FIG. 10) of pressure cup plate 210with membrane 304 adjacent recessed face 1000 of pressure cup plate 210.

Pressure cup plate 210, first gasket plate 308, thermal isolation plate212, second gasket plate 310, and valve manifold 214 are aligned using afirst dowel pin 316 and a second dowel pin (not shown). First dowel pin316 and the second dowel pin extend into bore 1012 in a back face 1100(shown with reference to FIG. 11) of pressure cup plate 210, throughrespective bores in first gasket plate 308, thermal isolation plate 212,and second gasket plate 310, and into a bore 1802 (shown with referenceto FIG. 18) in a front face 1800 (shown with reference to FIG. 18) ofvalve manifold 214 when the components are properly aligned. Pressurecup plate 210, first gasket plate 308, thermal isolation plate 212,second gasket plate 310, and valve manifold 214 are mounted adjacent toeach other in that order as shown with reference to FIG. 3. First gasketplate 308 is mounted adjacent back face 1100 of pressure cup plate 210.Back face 1100 of pressure cup plate 210 is generally parallel to andfaces in an opposite direction to front face 1000 of pressure cup plate210.

With reference to FIG. 4, a block diagram of a control system 400 of SMBsystem 100 is shown in accordance with an exemplary embodiment. Controlsystem 400 controls the operation of SMB system 100 to direct the flowof fluid in a manner that simulates a moving bed. Control system 400implements a desired process by controlling the states (open or closed)of the first plurality of valves 216 and the second plurality of valves217 of the left valve block assembly and right valve block assembly 200and by controlling the pumps that direct the flow of fluid in and out ofSMB system 100. The components of control system 400 may be mounted toor otherwise connect to electronics board 218. Control system 400 mayinclude an input interface 402, an output interface 404, acomputer-readable medium 406, a processor 408, and a controllerapplication 410.

Different and additional components may be incorporated into controlsystem 400. For example, control system 400 may further include acommunication interface. Components of control system 400 may be mountedto SMB system 100 or mounted in a separate device(s). As a result, thecommunication interface can provide an interface for receiving andtransmitting data between SMB system 100 and one or more additionaldevices hosting components of control system 400 using variousprotocols, transmission technologies, and media. The communicationinterface may support communication using various transmission mediathat may be wired or wireless. Thus, the components of control system400 may be connected as appropriate using wires or other couplingmethods or wirelessly and may be positioned at various locationsrelative to SMB system 100 including remote to SMB system 100.

Input interface 402 provides an interface for receiving information fromthe user for entry into control system 400 as known to those skilled inthe art. Input interface 402 may use various input technologiesincluding, but not limited to, a keyboard, a pen and touch screen, amouse, a track ball, a touch screen, a keypad, one or more buttons, etc.to allow the user to enter information into control system 400. SMBsystem 100 may have one or more input interfaces that use the same or adifferent interface technology.

Output interface 404 provides an interface for presenting informationfrom control system 400 to the user as known to those skilled in theart. For example, output interface 404 may include an interface to adisplay, a printer, a speaker, etc. The display may be a thin filmtransistor display, a light emitting diode display, a liquid crystaldisplay, or any of a variety of different displays known to thoseskilled in the art. The printer may be any of a variety of printers asknown to those skilled in the art. The speaker may be any of a varietyof speakers as known to those skilled in the art. Column statusindicator interface 112 is an output interface 404 of SMB system 100.SMB system 100 may have one or more output interfaces that use the sameor a different interface technology.

Computer-readable medium 406 is an electronic holding place or storagefor information so that the information can be accessed by processor 408as known to those skilled in the art. Computer-readable medium 406 caninclude, but is not limited to, any type of random access memory (RAM),any type of read only memory (ROM), any type of flash memory, etc. suchas magnetic storage devices (e.g., hard disk, floppy disk, magneticstrips, . . . ), optical disks (e.g., compact disk (CD), digitalversatile disk (DVD), . . . ), smart cards, flash memory devices, etc.SMB system 100 may have one or more computer-readable media that use thesame or a different memory media technology. SMB system 100 also mayhave one or more drives that support the loading of a memory media suchas a CD, a DVD, a flash memory card, etc.

Processor 408 executes instructions as known to those skilled in theart. The instructions may be carried out by a special purpose computer,logic circuits, or hardware circuits. Thus, processor 408 may beimplemented in hardware, firmware, software, or any combination of thesemethods. The term “execution” is the process of running an applicationor the carrying out of the operation called for by an instruction. Theinstructions may be written using one or more programming language,scripting language, assembly language, etc. Processor 408 executes aninstruction, meaning that it performs the operations called for by thatinstruction. Processor 408 operably couples with input interface 402,output interface 404, computer-readable medium 406, controllerapplication 410, etc. to receive, to send, and to process informationand to control the operations of SMB system 100. Processor 408 mayretrieve a set of instructions from a permanent memory device such as aROM device and copy the instructions in an executable form to atemporary memory device that is generally some form of RAM. SMB system100 may include a plurality of processors that use the same or adifferent processing technology.

Controller application 410 includes operations which control SMB system100 and may provide a graphical user interface with user selectable andcontrollable functionality to define the processes executed by SMBsystem 100. The operations may be implemented using hardware, firmware,software, or any combination of these methods. With reference to theexemplary embodiment of FIG. 4, controller application 410 isimplemented in software stored in computer-readable medium 406 andaccessible by processor 408 for execution of the computer-readableinstructions that embody the operations of controller application 410.The computer-readable instructions of controller application 410 may bewritten using one or more programming languages, assembly languages,scripting languages, etc. The functionality provided by controllerapplication 410 may be distributed among one or more modules and acrossone or more device. For example, controller application 410 may includea module that controls the opening and closing of the first plurality ofvalves 216 and the second plurality of valves 217 that is separate orintegrated with a module that controls pump flow rates. Controllerapplication 410 provides control signals to the plurality of electricalconnectors 220 which connect to the first plurality of valves 216 and tothe plurality of electrical connectors which connect to the secondplurality of valves 217 as well as to the pumps associated with theplurality of pump connectors 132.

The first plurality of valves 216 and the second plurality of valves 217are connected to a pressure reservoir providing a pressurized gas sourceand to a vent. For example, with reference to FIG. 4, a first valve 216a is shown connected to a first pressure reservoir 414 a and a firstvent 416 a, and a second valve 216 b is shown connected to a secondpressure reservoir 414 b and a second vent 416 b. First pressurereservoir 414 a and second pressure reservoir 414 b may be the same ordifferent. First vent 416 a and second vent 416 b may be the same ordifferent. The first plurality of valves 216 and the second plurality ofvalves 217 may be designed as normally open or may be designed asnormally closed. Controller application 410 can be designed to supporteither method of valve operation. In an exemplary embodiment, the firstplurality of valves 216 and the second plurality of valves 217 arenormally closed and are switched at 24 volts. To reduce heat, thevoltage applied to the first plurality of valves 216 and the secondplurality of valves 217 may be stepped down to 12 volts or lower afterswitching while maintaining the state.

With reference to FIG. 4, a simplified cross sectional view of a portionof valve block 300 is shown connected to first valve 216 a and to secondvalve 216 b to illustrate the operation of the valve states. Pressurecup plate 210 includes a first recess 420 a and a second recess 420 bcoupled to a first channel 424 a and a second channel 424 b,respectively. First channel 424 a and second channel 424 b operablycouple to first valve 216 a and to second valve 216 b, respectively.Fluidics stack assembly 302 includes a third channel 422 a and a fourthchannel 422 b. As shown with reference to FIG. 4, pneumatic pressurefrom second valve 216 b applied to membrane 304 through second channel424 b stops the flow of fluid through fourth channel 422 b. Pneumaticpressure released by first valve 216 a through first channel 424 acauses membrane 304 to deflect into first recess 420 a thereby allowingthe flow of fluid through third channel 422 a.

Membrane 304 is formed of a polymer that is sufficiently pliant topermit deflection when pneumatic pressure is relieved in a channel suchas first channel 424 a. In an exemplary embodiment, membrane 304 isformed of perfluoroalkoxy copolymer resin thermoplastic material havinga width of 0.01 inches though other materials and thicknesses may beused.

With reference to FIG. 5, a front view of port plate 202 is shown inaccordance with an exemplary embodiment. Port plate 202 may include aplurality of column port bores 500, a plurality of inlet port bores 502,a plurality of outlet port bores 504, and a plurality of connector bores506. The plurality of column port bores 500, the plurality of inlet portbores 502, the plurality of outlet port bores 504, and the plurality ofconnector bores 506 extend through a front face 508 of port plate 202and exit a back face of port plate 202. The plurality of column portbores 500, the plurality of inlet port bores 502, and the plurality ofoutlet port bores 504 have a smaller circumference on the back face ofport plate 202 than on front face 508 in the exemplary embodiment ofFIG. 5 though this is not necessary. The second plurality of column portconnectors 204 can be inserted in corresponding bores of the pluralityof column port bores 500. The plurality of inlet port connectors 206 canbe inserted in corresponding bores of the plurality of inlet port bores502. The plurality of outlet port connectors 208 can be inserted incorresponding bores of the plurality of outlet port bores 504. Theplurality of first connectors 312 can be inserted in corresponding boresof the plurality of connector bores 506.

In an exemplary embodiment, port plate 202 is formed of stainless steelmaterial having a width of 0.625 inches though other materials may beused. In the exemplary embodiment of FIG. 5, port plate 202 includeseight column port bores 500 to correspond with the eight column portconnectors 204, four inlet port bores 502 to correspond with the fourinlet port connectors 128, and four outlet port bores 504 to correspondwith the four outlet port connectors 130 though any number of bores maybe used depending on the application.

With reference to FIG. 6, a side perspective view of fluidics stackassembly 302 is shown in accordance with an exemplary embodiment. In theexemplary embodiment of FIG. 6, fluidics stack assembly 302 includes anI/O plate 600, a fluidics plate 602, and a seal plate 604. I/O plate 600includes first dowel pin bores 606. Fluidics plate 602 includes seconddowel pin bores 608. Seal plate 604 includes third dowel pin bores 610.Dowel pins 314 can be inserted in first dowel pin bores 606, seconddowel pin bores 608, and third dowel pin bores 610 to properly align I/Oplate 600, fluidics plate 602, and seal plate 604. In an exemplaryembodiment, I/O plate 600, fluidics plate 602, and seal plate 604 may beformed of thermoplastic material. In an exemplary embodiment, I/O plate600, fluidics plate 602, and seal plate 604 are diffusion bondedtogether after being properly aligned to form a single piece to minimizeor even eliminate any leakage between I/O plate 600, fluidics plate 602,and seal plate 604. For example, a diffusion bonding process such asthat provided by IDEX Corporation is used to diffusion bond I/O plate600, fluidics plate 602, and seal plate 604 together. Materials thatcould be contemplated for fluidics stack assembly 302 includepolyetherimide polyetheretherketone, polychloro-trifluoroethylene,polyphenylene sulfide, ethylene-tetrafluoroethylene, polyimide,ethylene-chlorotrifluoroethylene, pefluoroalkoxy,polytetrafluoroethylene, cyclic olefin copolymer, polyethylene,polyethylene, polyacetal, and acrylic. There are also forms of Teflon(fluorinated ethylene propylene, pefluoroalkoxy,polytetrafluoroethylene) filled with glass which could be used toimprove dimensional stability. I/O plate 600, fluidics plate 602, andseal plate 604 also could be manufactured by machining or injectionmolding. Other methods of bonding the layers together may includechemical adhesives, plasma etching, combinations of etching andadhesives, and laser bonding. Membrane 304 may also be bonded to sealplate 604 using similar technologies. A rubber or silicone membrane incombination with a fluidics stack assembly 302 formed of acrylic couldalso be contemplated for a lower pressure, lower cost biocompatibleunit. The fluidics stack assembly 302 and/or membrane 304 combinationmay be provided as a single-use disposable cartridge for crosscontamination-sensitive applications such as purification of proteinsfor therapeutic use.

I/O plate 600 may include a plurality of column port holes 612, aplurality of inlet port holes 614, and a plurality of outlet port holes614. The plurality of column port holes 612, the plurality of inlet portholes 614, and the plurality of outlet port holes 616 extend through afront face 618 of I/O plate 600 and exit a back face of I/O plate 600.In an exemplary embodiment, the plurality of column port holes 612, theplurality of inlet port holes 614, and the plurality of outlet portholes 614 have a diameter of 0.031 inches. In the exemplary embodimentof FIG. 5, I/O plate 600 includes eight column port holes 612 tocorrespond with the eight column port bores 500, four inlet port holes614 to correspond with the four inlet port bores 502, and four outletport holes 614 to correspond with the four outlet port bores 504 thoughany number of holes may be used depending on the application. The eightcolumn port holes 612 align with the eight column port bores 500, thefour inlet port holes 614 align with the four inlet port bores 502, andthe four outlet port holes 614 align with the four outlet port bores 504when I/O plate 600 is mounted to port plate 202.

With reference to FIG. 7, a front face 700 of fluidics plate 602 isshown in accordance with an exemplary embodiment. In the exemplaryembodiment of FIG. 7, fluidics plate 602 includes a second plurality ofcolumn port holes 702, a plurality of inlet port channels 704, and aplurality of outlet port channels 706. The second plurality of columnport holes 702 extend through front face 700 of fluidics plate 602 andexit a back face 800 (shown with reference to FIG. 8) of fluidics plate602. The second plurality of column port holes 702 align with theplurality of column port holes 612 of I/O plate 600 when I/O plate 600is bonded with or mounted to fluidics plate 602 using dowel pins 314.The plurality of inlet port channels 704 align with the plurality ofinlet port holes 614 of I/O plate 600 when I/O plate 600 is bonded withor mounted to fluidics plate 602 using dowel pins 314. The plurality ofoutlet port channels 706 align with the plurality of outlet port holes616 of I/O plate 600 when I/O plate 600 is bonded with or mounted tofluidics plate 602 using dowel pins 314.

A plurality of inlet holes 708 within each of the plurality of inletport channels 704 extend through front face 700 of fluidics plate 602and exit back face 800 of fluidics plate 602. A plurality of outletholes 710 within each of the plurality of outlet port channels 706extend through front face 700 of fluidics plate 602 and exit back face800 of fluidics plate 602. In an exemplary embodiment, the secondplurality of column port holes 702, the plurality of inlet holes 708,and the plurality of outlet holes 710 have a diameter of 0.031 inches.In an exemplary embodiment, the plurality of inlet port channels 704 andthe plurality of outlet port channels 706 have a width of 0.031 inchesand a depth of 0.031 inches with a rounded bottom. In the exemplaryembodiment of FIG. 7, fluidics plate 602 includes eight column portholes 702 to correspond with the eight column port holes 612 of I/Oplate 600, four inlet port channels 704 and four inlet holes 708 withineach inlet port channel to correspond with the four inlet port holes614, and four outlet port channels 706 and four outlet holes 710 withineach inlet port channel to correspond with the four outlet port holes616 though any number of holes may be used depending on the application.

With reference to FIG. 8, a back face 800 of fluidics plate 602 is shownin accordance with an exemplary embodiment. In the exemplary embodimentof FIG. 8, fluidics plate 602 includes a first plurality of channels 802and a second plurality of channels 804. The first plurality of channels802 each have an L-shape that extends between a first end 810 and asecond end 812. A corner channel 814 connects a first leg channel 816and a second leg channel 818 of the first plurality of channels 802forming a generally ninety degree angle though this is not required. Afirst subset of the second plurality of column port holes 702 extendthrough fluidics plate 602 at first end 810 of each of the firstplurality of channels 802. The second plurality of channels 804 eachhave a linear shape that extends between a first end 806 and a secondend 808. A second subset of the second plurality of column port holes702 extend through fluidics plate 602 at first end 806 of each of thesecond plurality of channels 804. The plurality of inlet holes 708 andthe plurality of outlet holes 710 form rows of holes in columns that areoffset from each other to align with the plurality of inlet portchannels 704 and the plurality of outlet port channels 706 on front face800, respectively. First leg channel 816 of the first plurality ofchannels 802 and the second plurality of channels 804 are generallyparallel to each other and to the rows formed by the plurality of inletholes 708 and the plurality of outlet holes 710. Second end 812 of thefirst plurality of channels 802 extends to a point in line with each rowformed by the plurality of inlet holes 708.

In an exemplary embodiment, the rows formed by the plurality of inletholes 708 and the rows formed by the plurality of outlet holes 710 areseparated by approximately 0.68 inches. In an exemplary embodiment, therows formed by the plurality of inlet holes 708 are separated from thesecond plurality of channels 804 by approximately 0.187 inches, and therows formed by the plurality of outlet holes 710 are separated from thefirst leg channel 816 of the first plurality of channels 802 byapproximately 0.187 inches. In an exemplary embodiment, the firstplurality of channels 802 and the second plurality of channels 804 havea width of approximately 0.031 inches and a depth of approximately 0.031inches with a rounded bottom. In the exemplary embodiment of FIG. 8,fluidics plate 602 includes four channels 802 and four channels 804 tocorrespond with the eight column port holes 702 though any number ofchannels may be used depending on the application.

With reference to FIG. 9, a front face 900 of seal plate 604 is shown inaccordance with an exemplary embodiment. In the exemplary embodiment ofFIG. 9, seal plate 604 includes a plurality of pairs of holes 902 thatare arranged in rows and columns. The plurality of pairs of holes 902extend through front face 900 of seal plate 604 and exit a back face ofseal plate 604. Each pair of the plurality of pairs of holes 902includes a first hole 904 positioned above a second hole 906 with firsthole 904 separated from second hole 906 by approximately 0.187 inches.Each pair of the plurality of pairs of holes 902 is arranged parallel tothe other pairs of the plurality of pairs of holes 902. The plurality ofpairs of holes 902 are arranged in rows and columns to align withelements of back face 800 of fluidics plate 602. In a first subset ofholes 908 of the plurality of pairs of holes 902, first hole 904 alignswith second end 812 of the first plurality of channels 802 and secondhole 906 aligns with second end 808 of the second plurality of channels804. In a second subset of holes 910 of the plurality of pairs of holes902, first hole 904 aligns with the plurality of outlet holes 710 andsecond hole 906 aligns with first leg channel 816 of the first pluralityof channels 802. In a third subset of holes 912 of the plurality ofpairs of holes 902, first hole 904 aligns with the plurality of inletholes 708 and second hole 906 aligns with the second plurality ofchannels 804. In an exemplary embodiment, the plurality of pairs ofholes 902 have a diameter of approximately 0.031 inches.

With reference to FIG. 10, recessed face 1000 and front face 1001 ofpressure cup plate 210 are shown in accordance with an exemplaryembodiment. In an exemplary embodiment, pressure cup plate 210 may beformed of stainless steel. In the exemplary embodiment of FIG. 10,recessed face 1000 of pressure cup plate 210 includes a plurality ofpressure cups 1002 that align with the plurality of pairs of holes 902that extend through the back face of seal plate 604. Each pressure cupof the plurality of pressure cups 1002 is centered inline with a centerof a pair of holes of the plurality of pairs of holes 902 when pressurecup plate 210 is aligned with seal plate 604. Membrane 304 is positionedbetween the back face of seal plate 604 and recessed face 1000 ofpressure cup plate 210. Each pressure cup of the plurality of pressurecups 1002 includes a recess 1300 (shown with reference to FIG. 13), afirst pressure port 1004, a second pressure port 1006, and an o-ringchannel 1008. In the exemplary embodiment of FIG. 10, pressure cup plate210 further includes dowel bores 1012 and a plurality of vent holes 1010that extend through recessed face 1000 and back face 1100 (shown withreference to FIG. 11). Dowel pins 314 mount in dowel bores 1012.

With reference to FIG. 11, a back face 1100 of pressure cup plate 210 isshown in accordance with an exemplary embodiment. In the exemplaryembodiment of FIG. 11, back face 1100 of pressure cup plate 210 includesa plurality of pairs of pressure ports 1102 that correspond with firstpressure port 1004 and second pressure port 1006 of each of theplurality of pressure cups 1002. Each pair of pressure ports of theplurality of pairs of pressure ports 1102 includes a third pressure port1104 that connects with first pressure port 1004 through a channelinternal to pressure cup plate 210 and a fourth pressure port 1106 thatconnects with second pressure port 1006 through a channel internal topressure cup plate 210.

With reference to FIG. 12, a cross section A-A (indicated in FIG. 10) ofpressure cup plate 210 is shown in accordance with an exemplaryembodiment. With reference to FIG. 13, a blowup of a section B(indicated in FIG. 12) of the cross section A-A of pressure cup plate210 is shown in accordance with an exemplary embodiment. In an exemplaryembodiment, recess 1300 has a maximum depth of approximately 0.01 inchesand a width in the plane of cross section A-A of 0.186 inches. In anexemplary embodiment, o-ring channel 1008 has a depth of approximately0.1 inches and a width of approximately 0.056 inches in the plane ofcross section A-A.

With reference to FIG. 14, a blowup of a section C (indicated in FIG.10) of pressure cup plate 210 is shown in accordance with an exemplaryembodiment. Second pressure port 1006 is positioned in o-ring channel1008. In an exemplary embodiment, recess 1300 has a length 1400 of 0.374inches. A vent channel 1402 extends between the plurality of pressurecups 1002 arranged in a row. Vent channel 1402 has a width ofapproximately 0.125 inches and a depth of 0.005 inches.

With reference to FIG. 15, a side, cutaway view of an o-ring 1500 of theplurality of o-rings 306 is shown in accordance with an exemplaryembodiment. With reference to FIG. 16, a cross section of o-ring 1500 ofthe plurality of o-rings 306 is shown in accordance with an exemplaryembodiment. Pneumatic pressure applied through second pressure port 1006holds o-ring 1500 of the plurality of o-rings 306 in place with anapproximately constant pressure. The o-ring 1500 is stably deformed intothe channel and against membrane 304 as a result of gas pressure throughsecond pressure port 1006, effectively sealing the perimeter of thepressure cup 1002 to prevent both gas leaks on the pneumatic side andfluid leaks between seal plate 604 and membrane 304 during operation ofSMB system 100. Thus, a seal exists on the gas side of membrane 304 thatis subjected to gas pressure provided by the first pressure system. Thehigh pressure gas “activates” the seal by causing o-ring 1500 to flareagainst the side walls of o-ring channel 1008 and to push againstmembrane 304 isolating the fluid port pressure from the gas portpressure. The pneumatic pressure on o-ring 1500 may be constant andindependent from the pneumatic pressure on membrane 304 provided by thesecond pressure system.

When the pneumatic pressure on membrane 304 exceeds the fluid backpressure, membrane 304 is forced against the plurality of pairs of holes902 of seal plate 604, which are surrounded by o-ring 1500 on theopposite side of membrane 304, preventing fluid flow between them. Whenthe fluid back pressure exceeds the pneumatic pressure on membrane 304,membrane 304 deflects into recess 1300 and fluid flow is allowed betweenthe plurality of holes, but prevented from flowing outside of the areasurrounded by o-ring 1500 By allowing fluid flow between the pluralityof pairs of holes 902 of seal plate 604, fluid flow can be providedbetween the plurality of outlet holes 710 and the first plurality ofchannels 802, between the plurality of inlet holes 708 and the secondplurality of channels 804, between the first plurality of channels 802and the second plurality of channels 804, through the second pluralityof column port holes 702 of fluidics plate 602, between the plurality ofinlet port holes 614 and the plurality of inlet port channels 704,between the plurality of outlet port holes 614 and the plurality ofoutlet port channels 706, and through the plurality of column port holes612 of I/O plate 600. Thus, by controlling the deflection of membrane304 at each pressure cup of the plurality of pressure cups 1002, fluidflow between the second plurality of column port connectors 204, theplurality of inlet port connectors 206, and the plurality of outlet portconnectors 208.

In an exemplary embodiment, o-ring 1500 is formed of an elastic materialsuch as rubber or soft plastic having a hardness of 80 Shore measuredusing a Shore A Durometer. Other materials having the same or differenthardness values may be used. For example, o-ring 1500 may be formed of aBuna N or Nitrile material that is a copolymer of butadiene andacrylonitrile. As another example, a chemically resistantfluoroelastomer material such as Perlast or polytetrafluoroethene may beused to form o-ring 1500. In an exemplary embodiment, o-ring 1500 has agenerally oval shape to correspond with o-ring channel 1008 and having awidth of approximately 0.502 inches, a length of approximately 0.314inches, and a depth of approximately 0.091 inches. The cross section ofo-ring 1500 has a generally U-shape with a first leg 1600, a second leg1602, and a body 1604 formed as a unitary piece, for example, using amolding process. First leg 1600 and second leg 1602 are pressed intoo-ring channel 1008 so that cup 1606 faces down into o-ring channel1008. First leg 1600 and second leg 1602 extend from first surface 1606of body 1604 forming a cup. In the exemplary embodiment of FIG. 16, thecup has a rounded bottom surface.

Body 1604 includes a first surface 1606, a second surface 1608, a thirdsurface 1610, and a fourth surface 1612. Second surface 1608 extendsfrom first surface 1606 at a first edge 1607. Third surface 1610 extendsfrom an opposite end of first surface 1606 at a second edge 1609. Fourthsurface 1612 extends from third surface 1610 at a third edge 1614.Fourth surface 1612 extends from second surface 1608 at a fourth edge1616. In the exemplary embodiment of FIG. 16, third edge 1614 and fourthedge 1616 are rounded and fourth surface 1612 protrudes away from body1604 relative to third edge 1614 and fourth edge 1616 by a first height1644. In an exemplary embodiment, first height 1644 is approximately0.01 inches. In an exemplary embodiment, body 1604 has a second height1642 between first surface 1606 and an edge of fourth surface 1612 ofapproximately 0.045 inches.

First leg 1600 includes a first leg interior surface 1618, a first legbottom surface 1620, and a first leg exterior surface 1622. First leginterior surface 1618 extends from first surface 1606 at a fifth edge1621. First leg bottom surface 1620 extends from first leg interiorsurface 1618 at a sixth edge 1624. First leg exterior surface 1622extends from first leg bottom surface 1620 at a seventh edge 1626 tofirst edge 1607. In the exemplary embodiment of FIG. 16, first legexterior surface 1622 extends from first edge 1607 forming an angle 1646relative to second surface 1608. In an exemplary embodiment, angle 1646is approximately five degrees. Thus, the angle formed between first legexterior surface 1622 and second surface 1608 is approximately 175degrees. In the exemplary embodiment of FIG. 16, fifth edge 1621 andsixth edge 1624 are rounded and seventh edge 1626 forms an approximatelyright angle. First leg 1600 extends from body 1604 by a third height1640 and has width between first leg interior surface 1618 and first legexterior surface 1622 of approximately 0.02 inches. In an exemplaryembodiment, third height 1640 is approximately 0.046 inches. In anexemplary embodiment, third height 1640 is greater than second height1642. First leg interior surface 1618 and first leg exterior surface1622 are generally parallel to each other. First leg bottom surface 1620is generally perpendicular to first leg exterior surface 1622.

Second leg 1602 includes a second leg interior surface 1626, a secondleg bottom surface 1628, and a second leg exterior surface 1630. Secondleg interior surface 1626 extends from first surface 1606 at an eighthedge 1623. Second leg bottom surface 1628 extends from second leginterior surface 1626 at a ninth edge 1632. Second leg exterior surface1630 extends from second leg bottom surface 1628 at a tenth edge 1634 tosecond edge 1609. In the exemplary embodiment of FIG. 16, second legexterior surface 1630 extends from second edge 1609 forming a secondangle 1648 relative to third surface 1610. In an exemplary embodiment,second angle 1648 is approximately five degrees. Thus, the angle formedbetween second leg exterior surface 1630 and third surface 1610 isapproximately 175 degrees. In the exemplary embodiment of FIG. 16,eighth edge 1623 and ninth edge 1632 are rounded and tenth edge 1634forms an approximately right angle. Second leg 1602 extends from body1604 by third height 1640 and has a width between second leg interiorsurface 1626 and second leg exterior surface 1630 of approximately 0.02inches.

With reference to FIG. 17, a front face 1700 of thermal isolation plate212 is shown in accordance with an exemplary embodiment. In an exemplaryembodiment, thermal isolation plate 212 is formed of a thermoplasticmaterial that provides a thermal barrier between pressure cup plate 210and valve manifold 214. In the exemplary embodiment of FIG. 9, thermalisolation plate 212 includes a second plurality of pairs of holes 1702that are arranged to align with the plurality of pairs of pressure ports1102 of pressure cup plate 210. The second plurality of pairs of holes1702 extend through front face 1700 of thermal isolation plate and exita back face of thermal isolation plate 212. First gasket plate 308 andsecond gasket plate 310 have a similar arrangement of holes when alignedwith thermal isolation plate 212. In an exemplary embodiment, firstgasket plate 308 and second gasket plate 310 are formed of anaramid-fiber-nitrile material that provides sealing of thermal isolationplate 212. Each pair of the second plurality of pairs of holes 1702includes a first hole 1704 positioned above a second hole 1706 withfirst hole 1704 separated from second hole 1706 by approximately 0.344inches. Each pair of the second plurality of pairs of holes 1702 isarranged parallel to the other pairs of the second plurality of pairs ofholes 1702. In an exemplary embodiment, the second plurality of pairs ofholes 1702 have a diameter of approximately 0.063 inches. In theexemplary embodiment of FIG. 17, thermal isolation plate 212 furtherincludes dowel bores 1708 that extend through front face 1700 and theback face of thermal isolation plate 212. Dowel pins 314 mount in dowelbores 1708.

With reference to FIG. 18, a front face 1800 of valve manifold 214 isshown in accordance with an exemplary embodiment. In an exemplaryembodiment, valve manifold 214 is formed of aluminum. In the exemplaryembodiment of FIG. 18, front face 1800 of valve manifold 214 includes asecond plurality of pairs of pressure ports 1802 that correspond withthe plurality of pairs of pressure ports 1102 of pressure cup plate 210.Each pair of pressure ports of the second plurality of pairs of pressureports 1802 includes a fifth pressure port 1804 that aligns with firstpressure port 1004 and third pressure port 1104 and a sixth pressureport 1806 that aligns with second pressure port 1006 and fourth pressureport 1106 thereby operably coupling the pressure ports.

With reference to FIG. 19, right side face 1900 of valve manifold 214 isshown in accordance with an exemplary embodiment. In an exemplaryembodiment, right side face 1900 of valve manifold 214 includes aplurality of valve connectors 1902 to which the first plurality ofvalves 216 are connected. Each valve connector of the plurality of valveconnectors 1902 includes a first pressure port 1904 and a secondpressure port 1906. First pressure port 1904 operably couples throughchannels within valve manifold 214 to a fifth pressure port 1804 of oneof the second plurality of pairs of pressure ports 1802 to providepneumatic pressure to first pressure port 1004 through third pressureport 1104 and fifth pressure port 1804. Second pressure port 1906provides the exhaust port for the corresponding valve of the firstplurality of valves 216. For example, when a valve opens the pressure isexhausted through second pressure port 1906 of the corresponding valve.In the exemplary embodiment of FIG. 19, right side face 1900 of valvemanifold 214 includes 20 valve connectors 1902 though any number ofvalve connectors may be used depending on the application.

With reference to FIG. 20, left side face 2000 of valve manifold 214 isshown in accordance with an exemplary embodiment. In an exemplaryembodiment, left side face 2000 of valve manifold 214 includes aplurality of valve connectors 2002 to which the second plurality ofvalves 217 are connected. Each valve connector of the plurality of valveconnectors 2002 includes a third pressure port 2004 and a fourthpressure port 2006. Third pressure port 2004 operably couples throughchannels within valve manifold 214 to a fifth pressure port 1804 of oneof the second plurality of pairs of pressure ports 1802 to providepneumatic pressure to first pressure port 1004 through third pressureport 1104 and fifth pressure port 1804. Fourth pressure port 2006provides the exhaust port for the corresponding valve of the secondplurality of valves 217. For example, when a valve opens the pressure isexhausted through fourth pressure port 2006. In the exemplary embodimentof FIG. 20, left side face 2000 of valve manifold 214 includes 16 valveconnectors 2002 though any number of valve connectors may be useddepending on the application.

With reference to FIG. 21, a back side face 2100 of valve manifold 214is shown in accordance with an exemplary embodiment. In an exemplaryembodiment, back side face 2100 of valve manifold 214 includes a firstpneumatic pressure connector 2102, a second pneumatic pressure connector2104, and a third pneumatic pressure connector 2106. First pneumaticpressure connector 2102 and second pneumatic pressure connector 2104 areconnected to the first plurality of valves 216 and the second pluralityof valves 217. First pneumatic pressure connector 2102 and secondpneumatic pressure connector 2104 provide pressure to the secondpneumatic pressure system through fifth pressure port 1804 of each ofthe second plurality of pairs of pressure ports 1802. In an exemplaryembodiment, first pneumatic pressure connector 2102 provides pressure tothe first plurality of valves 216, and second pneumatic pressureconnector 2104 provides pressure to the second plurality of valves 217.Third pneumatic pressure connector 2106 provides pressure to the firstpneumatic pressure system through sixth pressure port 1806 of each ofthe second plurality of pairs of pressure ports 1802 that aligns withsecond pressure port 1006 and fourth pressure port 1106 to hold o-ring1500 of the plurality of o-rings 306 in place. In an exemplaryembodiment, the first pneumatic pressure system is not connected to anyvalves, but includes a separate system of internal channels in valvemanifold 214 accessed by third pneumatic pressure connector 2106 fromthe rear of valve manifold 214.

Because the left valve block assembly and right valve block assembly 200are equivalent, except that the left valve block assembly is rotated 180degrees relative to the right valve block assembly 200, back side face2100 of valve manifold 214 also includes a fourth pneumatic pressureconnector 2108, a fifth pneumatic pressure connector 2110, and a sixthpneumatic pressure connector 2112. Fourth pneumatic pressure connector2108 and a fifth pneumatic pressure connector 2110 are connected to aplurality of valves that correspond to the first plurality of valves 216and the second plurality of valves 217 in the left block assembly. Sixthpneumatic pressure connector 2112 connects to the first pneumaticpressure system in the left block assembly. Thus, depending on whetherthe valve block assembly is mounted in the left or the right positionrelative to valve block panel 108, the bottom set of pneumatic pressureconnectors is used. Thus, fourth pneumatic pressure connector 2108 andfifth pneumatic pressure connector 2110 provide pressure to the secondpneumatic pressure system, and sixth pneumatic pressure connector 2112provides pressure to the first pneumatic pressure system when rightvalve block assembly 200 is rotated and used as the left valve blockassembly.

With reference to FIG. 22, the fluid flow between the left valve blockassembly and right valve block assembly 200 is shown in accordance withan exemplary embodiment. The functional elements of port plate 202 andfluidics stack assembly 302 of both the left valve block assembly andright valve block assembly 200 are shown with the ability to “seethrough” port plate 202 and fluidics stack assembly 302. Right valveblock assembly 200 includes the plurality of inlet port connectors 206,the plurality of outlet port connectors 208, the second plurality ofcolumn port connectors 204, the plurality of inlet port channels 704,the plurality of outlet port channels 706, the first plurality ofchannels 802, and the second plurality of channels 804. The left valveblock assembly includes a second plurality of inlet port connectors 206a, a second plurality of outlet port connectors 208 a, the firstplurality of column port connectors 126, a second plurality of inletport channels 704 a, a second plurality of outlet port channels 706 a, athird plurality of channels 802 a, and a fourth plurality of channels804 a.

With reference to the exemplary fluid flow configuration of FIG. 22, theplurality of inlet port connectors 206 includes a first inlet portconnector 2200 and a second inlet port connector 2202. First inlet portconnector 2200 is connected to a first container containing feed throughone of the four inlet port connectors 128. Second inlet port connector2202 is connected to a second container containing desorbent through asecond one of the four inlet port connectors 128. The plurality ofoutlet port connectors 208 includes a first outlet port connector 2204and a second outlet port connector 2206. First outlet port connector2204 is connected to a first container collecting extract through one ofthe four outlet port connectors 130. Second outlet port connector 2206is connected to a second container collecting raffinate through a secondone of the four outlet port connectors 130. The second plurality ofinlet port connectors 206 a includes a first inlet port connector 2200 aconnected to a first container containing feed through one of the fourinlet port connectors 128, and a second inlet port connector 2202 aconnected to a second container containing desorbent through a secondone of the four inlet port connectors 128. The second plurality ofoutlet port connectors 208 a includes a first outlet port connector 2204a connected to a first container collecting extract through one of thefour outlet port connectors 130, and a second outlet port connector 2206a connected to a second container collecting raffinate through a secondone of the four outlet port connectors 130.

The plurality of inlet port channels 704 includes a first inlet portchannel 2201 through which the feed flows and a second inlet portchannel 2203 through which the desorbent flows, and the plurality ofoutlet port channels 706 includes a first outlet port channel 2205through which the extract flows and a second outlet port channel 2207through which the raffinate flows. The second plurality of inlet portchannels 704 a includes a third inlet port channel 2201 a through whichthe feed flows and a fourth inlet port channel 2203 a through which thedesorbent flows, and the second plurality of outlet port channels 706 aincludes a third outlet port channel 2205 a through which the extractflows and a fourth outlet port channel 2207 a through which theraffinate flows.

The first plurality of channels 802 connect to the second plurality ofcolumn port connectors 204 which connect to an output side of a column.The second plurality of channels 804 connect to the second plurality ofcolumn port connectors 204 which connect to an input side of a column.The third plurality of channels 802 a connect to the first plurality ofcolumn port connectors 126 which connect to an input side of a column.The fourth plurality of channels 804 a connect to the first plurality ofcolumn port connectors 126 which connect to an output side of a column.In the exemplary embodiment of FIG. 22, SMB system 100 includes a firstcolumn 2208, a second column 2210, a third column 2212, a fourth column2214, a fifth column 2216, a sixth column 2218, a seventh column 2220,and an eighth column 2222.

As an example to illustrate fluid flow between right valve blockassembly 200 and the left valve block assembly, feed flows into firstinlet port connector 2200 under control of a pump and into first inletport channel 2201. If the valve associated with a first inlet hole 2224opens, the feed flows between first hole 904 and the correspondingsecond hole 906 and into a first channel 2227 of the second plurality ofchannels 804. First channel 2227 flows into a first column portconnector 2244 of the second plurality of column port connectors 204 ifthe remaining valves associated with first channel 2227 are closed,through first column 2208, into a second column port connector 2246 ofthe first plurality of column port connectors 126, and onto a secondchannel 2227 a of the fourth plurality of channels 804 a. The feed canthen flow onto one of the second plurality of outlet port channels 706 aor onto a third channel 2232 of the third plurality of channels 802 a.For example, if the valve associated with a first outlet hole 2228opens, the feed flows between first hole 904 and the correspondingsecond hole 906 and into a fourth channel 2234 of the plurality ofoutlet port channels 706 a and out of first outlet port connector 2204a.

As another example, second channel 2227 a can connect to third channel2232 of the third plurality of channels 802 a by opening the valveassociated with an end 2231 of second channel 2227 a and an end 2233 ofthird channel 2232. Such a valve can thus act as a shutoff betweencolumns. End 2231 of second channel 2227 a corresponds to a second end808 of a channel of the fourth plurality of channels 804 a. End 2233 ofthird channel 2232 corresponds to a second end 812 of a channel of thethird plurality of channels 802 a. First hole 904 and the correspondingsecond hole 906 associated with end 2233 of third channel 2232 and end2231 of second channel 2227 a, respectively, are part of the firstsubset of holes 908 of the plurality of pairs of holes 902. If feedflows onto third channel 2232, the feed flows through a third columnport connector 2248 of the first plurality of column port connectors126, through second column 2210, into a fourth column port connector2250 of the second plurality of column port connectors 204, and onto afourth channel 2229 of the first plurality of channels 802. In thismanner, fluid flow into the plurality of inlet port channels 704, out ofthe plurality of outlet port channels 706, and through the plurality ofcolumns can be controlled in any number of ways by opening and closingthe appropriate valves. Eighth column 2222 connects between a fifthcolumn port connector 2252 of the first plurality of column portconnectors 126 and a sixth column port connector 2254 of the secondplurality of column port connectors 204 to provide a continuous loopacross the plurality of columns.

Thus, each column of the plurality of columns has a total of nine valvesassociated with it: four to control flow from the plurality of inletport channels 704 (the second plurality of inlet port channels 704 a);four to control flow to the plurality of outlet port channels 706 (thesecond plurality of outlet port channels 706 a); and one shutoff valvewhich controls flow between the first plurality of channels 802 and thesecond plurality of channels 804 (the third plurality of channels 802 aand the fourth plurality of channels 804 a). Fluid flows into thefluidics system through one of the plurality of inlet port connectors206 (the second plurality of inlet port connectors 206 a) and migratesthrough the fluidics system depending on which valve ports are open.

The valve block assemblies disclosed herein may be configured for avariety of separation modes. In one aspect, the assemblies areconfigured for standard SMB. Standard SMB involves the use of two inletports (feed, desorbent) and two outlet ports (extract, raffinate). Fourchromatographic zones may be established as determined by the locationof the inlet and outlet ports. Zone 1 is defined as the zone between thedesorbent inlet and the extract outlet. Zone 2 is defined as the zonebetween the extract outlet and the feed inlet. Zone 3 is defined as thezone between the feed inlet and raffinate outlet. Zone 4 is defined asthe zone between the raffinate outlet and desorbent inlet. In standardSMB, all zones are connected to form a continuous loop. By way ofexample only, in an eight-column system (as shown in FIG. 22) with twocolumns in each zone, a total of twelve valves would be open at any onetime in the cycle: the desorbent, extract, feed, and raffinate valvesand the eight shutoff valves.

In a variation on standard SMB mode, certain chromatographic zones maybe eliminated by closing the appropriate shutoff valves. By way ofexample only, Zone 4 may be eliminated by closing the shutoff valvebetween Zones 1 and 3. In an eight-column system (as shown in FIG. 22),with three columns in Zone 1, two columns in Zone 2, and three columnsin Zone 3, a total of eleven valves would be open at any one time: thedesorbent, extract, feed, and raffinate valves and seven shutoff valves(the shutoff valve between Zones 1 and 3 is closed).

In another aspect, the assemblies are configured for step protocols. Bystep protocols, it is meant that one or more isolated chromatographiczones are established in the assembly by closing the appropriate shutoffvalves and activating additional pumps. Isolation of chromatographiczones enables the flow rate and other separation conditions of one zoneto be adjusted independently of another zone. By way of example only, inan eight-column system (as shown in FIG. 22), with two columns in eachzone and four isolated zones, a total of twelve valves would be open atany one time during the separation cycle: the feed, desorbent, Aux 1 IN,Aux 2 IN, extract, raffinate, Aux 1 OUT, Aux 2 OUT, and four shutoffvalves (the shutoff valves between each zone are closed). Aux 1 IN andAux 2 IN may be provided by the remaining inlet port connectors of theplurality of inlet port connectors 128, and Aux 1 OUT and Aux 2 OUT maybe provided by the remaining outlet port connectors of the plurality ofoutlet port connectors 130. As an example, continuous step protocols canbe devised by switching the column ports at periodic intervals analogousto SMB mode operation.

In another aspect, the assemblies are configured to incorporate one ormore additional pumps to control internal zone flow rates. During SMBseparations, multiple pumps may be employed to control flow rates ofexternal inlet and outlet streams, as well as internal zone flow rates.By way of example, in many SMB systems a recirculating pump is employedin zone 4 to conserve desorbent and enable greater concentration ofextract and raffinate solutes. Following this example, SMB system 100can incorporate an internal recirculating pump into an SMB protocol byconnecting an Aux 1 OUT outlet connector to the inlet side of a pump,connecting the pump outlet to an Aux 2 IN inlet port connector, closingthe shutoff valve of a column in zone 4, opening the same column's Aux 1OUT valve, and opening the downstream column's Aux 2 IN valve.Activating this pump in the SMB cycle provides the greater ability tocontrol the flow rate for desorbent in zone 4 that is pumped into zone1. Similar internal flow loops may be employed in other zones.

In yet another aspect, the assemblies are configured for a combinationof standard SMB and step protocols. By way of example only, an isolatedzone may be included in a two-column section of an eight-column system,with the other six employed in standard SMB mode. The isolatedtwo-column section may be used for cleaning the columns.

In yet another aspect, the assemblies are configured for gradientprotocols. By gradient protocols, it is meant that one or morechromatographic zones are established in which solvent gradients areapplied through the use of multiple pump heads and standard mixingprocedures. For example, a linear salt gradient can be created bypumping two source solutions containing different salt concentrationsthrough a mixer and into a system inlet port. During the process, theratio of the source solutions is continuously adjusted by varying thepump flow rates via programming software to enable the formation of anincreasing or decreasing salt concentration in the solvent delivered tothe system.

In yet a further aspect, the assemblies are configured for standard,fixed-bed column chromatography. By opening and closing appropriatevalves, a single column or multiple columns may also be run on SMBsystem 100 using standard protocols known in the art. By way of exampleonly, from one to eight columns could be employed in a non-continuousmode by opening one appropriate inlet upstream of the first column, theappropriate shutoff valves, and one outlet valve downstream of the lastcolumn. Input solutions (for example feedstock, wash solutions,desorbent, salt gradients, pH gradients, regeneration solutions) can bepumped sequentially through the column series to effect separation.

Any of these separation modes may be combined with the appropriatecolumn types to achieve virtually any type of liquid chromatographicseparation, including, but not limited to affinity chromatography,ion-exchange chromatography, size exclusion chromatography, andhydrophobic interaction chromatography.

With reference to FIG. 23, a front side, perspective view of column rackassembly 120 is shown in accordance with an exemplary embodiment. Columnrack assembly 120 may include a rack 2300, a mounting plate 2302, aplurality of clamping drawers 2304, a plurality of springs 2306, and aplurality of spring blocks 2308. In an exemplary embodiment, rack 2300may be formed of nylon. In the exemplary embodiment of FIGS. 1 and 23,column rack assembly 120 provides mounting locations for eightchromatographic columns. As a result, column rack assembly 120 includeseight clamping drawers, eight springs, and eight spring blocks.

With reference to FIG. 24, a back side, perspective view of column rackassembly 120 is shown in accordance with an exemplary embodiment. Columnrack assembly 120 may further include a plurality of plate mountingscrews 2400, a plurality of spring block screws 2402, and a plurality ofspring block mounting screws 2404. The plurality of plate mountingscrews 2400 mount rack 2300 to mounting plate 2302. The plurality ofspring block screws 2402 mount a spring of the plurality of springs 2306to a spring block of the plurality of spring blocks 2308 such that eachspring is mounted to a spring block using a nut 2403. A spring of theplurality of springs 2306 is positioned on or mounted to extend aroundeach of the plurality of spring block screws 2402. In an exemplaryembodiment, the spring may be a compression spring having a compressionforce of three pounds per inch. The plurality of spring block mountingscrews 2404 mount a spring block of the plurality of spring blocks 2308to a clamping drawer of the plurality of clamping drawers 2304 such thateach spring block is mounted to a clamping drawer.

With reference to FIG. 25, a front side, perspective view of mountingplate 2302 of column rack assembly 120 is shown in accordance with anexemplary embodiment. In an exemplary embodiment, mounting plate 2302may be formed of nylon. Mounting plate 2302 may include a firstplurality of mounting holes 2500, a second plurality of mounting holes2501, a plurality of slots 2502, and a plurality of spring through-holes2504. The plurality of plate mounting screws 2400 extend through thefirst plurality of mounting holes 2500 to mount rack 2300 to mountingplate 2302. A second plurality of mounting screws (not shown) extendthrough the second plurality of mounting holes 2501 to mount column rackassembly 120 to valve block panel 108. A clamping drawer of theplurality of clamping drawers 2304 fits through a slot of the pluralityof slots 2502. A spring of the plurality of springs 2306 extends througha spring through-hole of the plurality of spring through-holes 2504. Inthe exemplary embodiment of FIG. 25, mounting plate 2302 includes eightslots and eight spring through-holes.

With reference to FIG. 26, a top side, perspective view of a clampingdrawer 2600 of the plurality of clamping drawers 2304 is shown inaccordance with an exemplary embodiment. Clamping drawer 2600 mayinclude a first plate 2602, a second plate 2604, and a third plate 2606.First plate 2602 includes a first edge 2609 and a second edge 2616opposite first edge 2608. Second plate 2604 includes a third edge 2611and a fourth edge 2612 opposite third edge 2611. Third plate 2606includes a fifth edge 2614. A first corner 2608 mounts second plate 2604to first plate 2602 such that second plate 2604 extends in a generallyperpendicular direction between first edge 2609 of first plate 2602 andthird edge 2611 of second plate 2604. A second corner 2610 mounts thirdplate 2606 to second plate 2604 such that third plate 2606 extends fromsecond plate 2604 between fourth edge 2612 of second plate 2604 andfifth edge 2614 of third plate 2606. Clamping drawer 2600 may be formedof a single or multiple pieces of material without limitation. In anexemplary embodiment, clamping drawer 2600 is formed of stainless steel,and second corner 2610 forms an approximately 70 degree angle betweenthird plate 2606 and second plate 2604 such that third plate 2606extends from second plate 2604 in a direction opposite the directionthat first plate 2602 extends from second plate 2604. First plate 2602further includes a plurality of holes 2618 though a single hole may beused. One or more of the plurality of spring block mounting screws 2404extend through the plurality of holes 2618 of each clamping drawer 2600to mount clamping drawer 2600 to a spring block of the plurality ofspring blocks 2308.

With reference to FIG. 27, a cross-sectional view of rack 2300 of columnrack assembly 120 is shown in accordance with an exemplary embodiment.Rack 2300 may include a plurality of shelves 2700. In the exemplaryembodiment of FIG. 25, rack 2300 includes eight shelves which have agenerally triangular cross sectional shape though other shapes may beused including circular and rectangular. Associated with each of theplurality of shelves 2700 may be a spring channel 2702 and a clampingdrawer channel 2704. Spring channel 2702 may include a first channelportion 2706 and a second channel portion 2708 which abut each other ata transition channel portion 2710. First channel portion 2706 has alarger diameter than second channel portion 2708. First channel portion2706 is sized and shaped to accommodate a spring of the plurality ofsprings 2306. Second channel portion 2708 is sized and shaped toaccommodate a spring block screw of the plurality of spring block screws2402, but not to accommodate a spring of the plurality of springs 2306.Thus, an end of a spring of the plurality of springs 2306 is positionedto press against transition channel portion 2710 between first channelportion 2706 and second channel portion 2708. Clamping drawer channel2704 is sized and shaped to accommodate clamping drawer 2600.

With reference to FIG. 28, a front, skeleton view of spring block 2308of column rack assembly 120 is shown in accordance with an exemplaryembodiment. With reference to FIG. 29, a bottom, skeleton view of springblock 2308 is shown in accordance with an exemplary embodiment. Withreference to FIGS. 28 and 29, spring block 2308 may include a front face2800, a second spring channel 2801, a first mounting screw channel 2808,a second mounting screw channel 2810, and a bottom face 2900. Front face2800 may include second spring channel 2801. Second spring channel 2801extends through spring block 2308 from front face 2800 to a back face(not shown). Second spring channel 2801 may include a first channelportion 2802, a second channel portion 2804, a third channel portion2806, and a fourth channel portion 2807 which abut each other to form asingle channel having different diameters. First channel portion 2802has a sloped wall which slopes from a first diameter to a seconddiameter that is smaller in diameter than the first diameter. Secondchannel portion 2804 has the second diameter. Third channel portion 2806has a second sloped wall which slopes from the second diameter to athird diameter that is smaller in diameter than the second diameter.Fourth channel portion 2807 has the third diameter. First channelportion 2802 and second channel portion 2804 are sized and shaped toaccommodate a spring of the plurality of springs 2306. Third channelportion 2806 and fourth channel portion 2807 are sized and shaped toaccommodate a spring block screw of the plurality of spring block screws2402, but not to accommodate a spring of the plurality of springs 2306.Thus, an end of a spring of the plurality of springs 2306 is positionedto press against third channel portion 2806.

Bottom face 2900 may include first mounting screw channel 2808 and asecond mounting screw channel 2810. First mounting screw channel 2808and a second mounting screw channel 2810 extend into spring block 2308on either side of second spring channel 2801. First mounting screwchannel 2808 and a second mounting screw channel 2810 are sized andshaped to accommodate a spring block mounting screw of the plurality ofspring block mounting screws 2404 to mount spring block 2308 andclamping drawer 2600 together.

Thus, a spring of the plurality of springs 2306 is mounted at one end torack 2300 and at the other end to spring block 2308. Spring block 2308is further mounted to clamping drawer 2600 which extends throughclamping drawer channel 2704 of rack 2300 and through a slot of theplurality of slots 2502 of mounting plate 2302. Due to the tension ofthe spring, clamping drawer 2600 is held against rack 2300 in a shelf ofthe plurality of shelves 2700. A user can withdraw clamping drawer 2600by pulling against the tension of the spring and position achromatographic column within the shelf. The user releases clampingdrawer 2600 which holds the chromatographic column in position againstrack 2300. Column rack assembly 120 can accommodate a variety ofdifferently sized and shaped chromatographic columns.

The word “exemplary” is used herein to mean serving as an example,instance, or illustration. Any aspect or design described herein as“exemplary” is not necessarily to be construed as preferred oradvantageous over other aspects or designs. Further, for the purposes ofthis disclosure and unless otherwise specified, “a” or “an” means “oneor more”. The exemplary embodiments may be implemented as a method,machine, or article of manufacture using standard programming and/orengineering techniques to produce software, firmware, hardware, and/orany combination thereof to control a device to implement the disclosedembodiments.

The foregoing description of exemplary embodiments of the invention havebeen presented for purposes of illustration and of description. It isnot intended to be exhaustive or to limit the invention to the preciseform disclosed, and modifications and variations are possible in lightof the above teachings or may be acquired from practice of theinvention. The embodiments were chosen and described in order to explainthe principles of the invention and as practical applications of theinvention to enable one skilled in the art to utilize the invention invarious embodiments and with various modifications as suited to theparticular use contemplated. It is intended that the scope of theinvention be defined by the claims appended hereto and theirequivalents.

1. A valve block assembly comprising: a fluidics stack assemblycomprising: an input/output (I/O) plate comprising an inlet port holeextending through the I/O plate and an outlet port hole extendingthrough the I/O plate; a fluidics plate comprising: a first surfacecomprising an inlet channel formed in the first surface and an outlethole extending through the fluidics plate, wherein the inlet channelincludes an inlet hole extending through the fluidics plate; and asecond surface comprising the inlet hole, the outlet hole, and a firstchannel formed in the second surface; and a seal plate comprising afirst hole extending through the seal plate and a second hole extendingthrough the seal plate; a membrane; and a pressure cup plate comprisinga pressure cup, wherein the pressure cup comprises: an o-ring; a channelformed in a surface of the pressure cup plate to surround a firstportion of the surface, wherein the channel is configured to hold theo-ring; and a first pressure port extending through a body and openinginto the first portion of the surface; and wherein the fluidics stackassembly, the membrane and the surface of the pressure cup plate arealigned and mounted to form a sealing surface between the I/O plate andthe fluidics plate, between the fluidics plate and the seal plate,between the seal plate and the membrane, and between the membrane andthe surface of the pressure cup plate; and further wherein, whenaligned, the inlet port hole aligns with the inlet channel, the inlethole aligns with the first hole, the outlet port hole aligns with theoutlet hole, and the second hole aligns with the first channel, and thefirst portion of the surface of the pressure cup plate surrounds thefirst hole and the second hole to support fluid communication betweenthe inlet port hole and the outlet port hole under control of pressurechanges within the first pressure port.
 2. The valve block assembly ofclaim 1, further comprising a second pressure port extending through thebody and opening into the channel of the pressure cup, wherein apneumatic pressure within the second pressure port is controlled to holdthe o-ring in the channel when a second pressure within the firstpressure port changes.
 3. The valve block assembly of claim 1, furthercomprising a vent channel formed in the surface of the body to extendbetween the channel of the pressure cup and a hole or edge of thepressure cup plate.
 4. The valve block assembly of claim 1, wherein theI/O plate, the fluidics plate, and the seal plate are diffusion bondedtogether.
 5. The valve block assembly of claim 1, wherein the I/O platefurther comprises a second inlet port hole extending through the I/Oplate and a second outlet port hole extending through the I/O plate. 6.The valve block assembly of claim 5, wherein the first surface of thefluidics plate further comprises a second inlet channel formed in thefirst surface and a second outlet hole extending through the fluidicsplate, wherein the second inlet channel includes a second inlet holeextending through the fluidics plate.
 7. The valve block assembly ofclaim 6, wherein the second surface of the fluidics plate furthercomprises the second inlet hole, the second outlet hole, and a secondchannel formed in the second surface, wherein the second channelincludes the second inlet hole.
 8. The valve block assembly of claim 7,wherein the seal plate further comprises a third hole extending throughthe seal plate and a fourth hole extending through the seal plate. 9.The valve block assembly of claim 8, wherein, when aligned, the secondinlet port hole aligns with the second inlet channel, the second inlethole aligns with the fourth hole, the second outlet port hole alignswith the second outlet hole, and the third hole aligns with the secondchannel to support fluid communication between the second inlet porthole and the second outlet port hole.
 10. The valve block assembly ofclaim 9, wherein the seal plate further comprises a fifth hole extendingthrough the seal plate and a sixth hole extending through the sealplate.
 11. The valve block assembly of claim 10, wherein, when aligned,the fifth hole aligns with the second channel of the fluidics plate andthe sixth hole aligns with the first channel of the fluidics plate tosupport fluid communication between the inlet port hole and the outletport hole.
 12. A valve block assembly comprising: a fluidics stackassembly comprising: an input/output (I/O) plate comprising: an inletport hole extending through the I/O plate and an outlet port holeextending through the I/O plate; and a first surface comprising anoutlet hole extending through the I/O plate; a fluidics plate comprisingan inlet hole and an outlet hole extending through the fluidics plate; aseal plate comprising a first hole extending through the seal plate; aninlet channel comprising an inlet port hole extending through the I/Oplate; and a first channel comprising a second hole extending throughthe fluidics plate; a membrane; and a pressure cup plate comprising apressure cup, wherein the pressure cup comprises an o-ring; a channelformed in a surface of the pressure cup plate to surround a firstportion of the surface, wherein the channel is configured to hold theo-ring; and a first pressure port extending through the body and openinginto the first portion of the surface; and wherein the fluidics stackassembly, the membrane, and the surface of the pressure cup plate arealigned and mounted to form a sealing surface between the I/O plate andthe fluidics plate, between the fluidics plate and the seal plate,between the seal plate and the membrane, and between the membrane andthe surface of the pressure cup plate.
 13. The valve block assembly ofclaim 12, wherein the inlet channel is formed in the first surface ofthe I/O plate.
 14. The valve block assembly of claim 12, wherein thefirst channel is formed in a surface of the seal plate.
 15. The valveblock assembly of claim 12, wherein the inlet channel is formed in asurface of the fluidics plate.
 16. The valve block assembly of claim 12,wherein a first portion of the inlet channel is formed in the firstsurface of the I/O plate and a second portion of the inlet channel isformed in a surface of the fluidics plate.
 17. The valve block assemblyof claim 12, wherein a first portion of the first channel is formed in asurface of the seal plate and a second portion of the first channel isformed in a surface of the fluidics plate.
 18. The valve block assemblyof claim 12, wherein the first channel is formed in a surface of thefluidics plate.